Recent progress in marine natural products with 1,2-oxazine scaffold: structural diversity, biological potential and synthetic studies.

The 1,2-oxazine moiety, characterized by a directly linked N-O bond within a six-membered ring scaffold, benefits from the presence of oxygen and nitrogen heteroatoms to possess a high density of lone-pair electrons and a polarized ring system. These structural features optimize its physical properties and drug-likeness, thus rendering 1,2-oxazine a highly promising chemical scaffold for the discovery and development of bioactive lead compounds. Since the discovery of the first 1,2-oxazine-containing marine natural product (1,2-oxazine MNP) in 1986, a total of 56 naturally occurring 1,2-oxazine MNPs have been isolated and characterized. This review presents a systematic summary of the 1,2-oxazine MNP chemical family, with a primary focus on elaborating their source organisms, structural diversities, bioactivities, structure-activity relationship (SAR), mechanisms of action, chemical synthesis, and biosynthesis.